Biomineralization is the physiological process by which soluble constituents of the extracellular fluid, principally calcium, phosphate and carbonate, are brought together under conditions which favor the formation of a crystalline structure. This process is found throughout the animal kingdom, ranging from shell formation in some invertebrates to bone and tooth development among vertebrates. Abnormal bone demineralization is a common and often disabling condition affecting the elderly, individuals of any age subjected to prolonged bed rest and those who venture into space under weightless conditions. For decades, the importance of normal and abnormal mineralization has been recognized, yet the fundamental transport mechanisms underlying mineralization demineralization are obscure. A comprehensive model for these processes must include a detailed description of the membrane transport mechanisms found in those cells responsible for calcium mineralization. Preliminary data have been obtained supporting the use of the mantle epithelium of the freshwater clam, Unio, as a model for biomineralization. This polarized epithelial tissue is responsible for the calcium mineralization of the shell. It possesses many characteristics similar to mineralizing tissues found in higher animals without the serious disadvantage of a complicated morphology. The simple morphology of the planar mantle epithelium can be easily manipulated in the laboratory to stimulate conditions which favor either demineralization or mineralization. The first phase of this project will be a characterization of the mantle epithelium, including the measurements of the transepithelial open-circuit potential, the short-circuit current, tissue conductance, and radioisotope fluxes of Ca++, Na+, K+, and Cl-. The results of these experiments will permit discrimination between passive and active transepithelial transport mechanisms for each ion species. In the second phase of the project, intracellular microelectrodes will be employed to measure the electrical potential profile across the mantle epithelium, the conductance ratio of the mineral-facing-membrane to the blood-facing-membrane, and the intracellular ionic activities under conditions which favor either mineralization or demineralization. Taken together, the results of these studies will permit the development of a model for biomineralization that includes the membrane transport mechanisms that control this process.